Plateau in body habitus changes and serum lipid abnormalities in HIV-positive women on highly active antiretroviral therapy: a 3.5-year study.

BACKGROUND: In a previously reported study, 21 women (propositi) who reported changes in body habitus during highly active antiretroviral therapy (HAART) were evaluated and compared with 21 women (comparison group) on HAART who did not report body habitus changes. Mean durations of HAART at baseline evaluation were 12.5 and 15.2 months for the propositi and comparison group, respectively. OBJECTIVE: Follow-up of the propositi and comparison group was conducted to determine whether body habitus changes and lipid abnormalities are progressive, stable, or improved with time and alteration of the HAART regimen. METHODS: Patients were evaluated by standardized interview, physical examination, body weight, body mass index, CD4 cell count, plasma HIV RNA levels, and lipid profiles. RESULTS: Fourteen of 21 propositi were available for follow-up. The mean duration of HAART was 42.7 months; body habitus changes were stable in 10 of the 14 women. Thirteen of 21 women in the comparison group were available for follow-up after a mean duration of HAART of 38.5 months; 2 of the 13 women had developed body habitus changes at follow-up. In both groups, mean serum lipid values at follow-up remained elevated to levels associated with increased cardiovascular risk. CONCLUSIONS: Body habitus changes in women most often developed within 1 year of initiation of HAART. Changes were largely stable after 2.5 additional years of HAART. Only modest and inconsistent improvement was achieved with alteration in the HAART regimen. Serum lipid abnormalities evident within the first year of HAART were also stable with 2.5 additional years of therapy.

Lipoprotein response to a National Cholesterol Education Program step II diet with and without energy restriction.

This study examined the efficacy of a National Cholesterol Education Program (NCEP) step II diet (25% fat with < 7% saturated fat [SFA]) with and without moderate energy restriction. We tested the hypothesis that moderate energy restriction would improve the lipid profile resulting from an isoweight NCEP step II diet. Twenty hypercholesterolemic subjets (10 men and 10 postmenopausal women) consumed the following three controlled diets, each of 4 weeks' duration, as outpatients: (1) high-fat, high-saturated-fat diet to establish baseline lipids and isoweight energy requirements, (2) NCEP step II diet at isoweight energy, and (3) NCEP step II diet with an energy level 15% less than isoweight. The NCEP step II diet at isoweight energy reduced total cholesterol (TC) by 4% (P = .015), high-density lipoprotein cholesterol (HDL-c) by 13% (P < .0001), and HDL2-c by 40% (P < .0001). The TC:HDL-c ratio increased from 4.9 to 5.5 (P < .0001) and was increased in 19 of 20 subjects. Apolipoprotein B (apo B)-containing lipoproteins changed reciprocally: low-density lipoprotein cholesterol (LDL-c) decreased 4% (P = .008) and very-low-density lipoprotein cholesterol (VLDL-c) increased 29% (P < .0001). Apo B levels did not change. Compared with the NCEP isoweight diet the NCEP hypocaloric diet significantly reduced VLDL-c (-9%, P = .014) and apo B (-5%, P = .015). There was an additional reduction in TC (-4%, P = .073) and LDL-c (-4%, P = .126) with no change in HDL-c (P = .807). These data indicate that a NCEP step II diet with energy restriction produces a more desirable lipoprotein response than a NCEP step II isoweight diet. Neither NCEP step II diet improved the TC:HDL-c ratio.

Changes in body habitus and serum lipid abnormalities in HIV-positive women on highly active antiretroviral therapy (HAART).

Twenty-one women (propositi) who expressed serious concerns about changes in body habitus during highly active antiretroviral therapy (HAART) were evaluated by thorough physical examination, anthropometric measurements, and serum lipid and endocrine assays. The same evaluations were carried out in a comparison group of 21 women who received HAART but did not complain of changes in habitus. No significant demographic differences were found between the propositi and the comparison group, nor were there significant differences in CD4 count or plasma viral load (PVL) between the two groups. Lipid analyses were also performed on plasma obtained prior to HAART from 12 of the women. The frequency of changes reported by the 21 propositi were increase in abdominal size (90%), increase in breast size (71%), weight gain of >5 kg (43%), peripheral fat wasting (43%), buttock fat wasting (38%) and development of cervicodorsal fat pad (19%). A subset of patients in the comparison group experienced increase in abdominal size (29%) and weight gain >5 kg (19%), but none experienced clinically detectable peripheral or buttock fat wasting, increased breast size, or development of cervicodorsal fat pads. Mean waist circumference, waist-to-hip ratios (WHR), body fat, and body mass index (BMI) were above the desirable range for women in both propositi and the comparison group. Levels of total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol associated with increased cardiovascular risk were found in 48%, 62%, 45%, and 33%. respectively, of the propositi, with similar findings in the comparison group. Fasting insulin levels were elevated in 4 propositi and 6 of the comparison group; mean insulin levels were within the normal range for both groups. In the comparison of lipids for the subset of patients before and after HAART therapy, HAART was associated with significant increases in total cholesterol, apolipoprotein B, and HDL cholesterol. Changes in body habitus caused by redistribution of fat occur commonly in women receiving HAART. Serum lipid abnormalities also are common during HAART and appear to be as frequent in women who do not experience clinically apparent body fat redistribution as in those who do. The observed changes in body fat distribution and in serum lipid levels are alterations that have been strongly correlated with increased risk for cardiovascular disease. Therefore, an understanding of the basis of these phenomena, and the risks with which they may be associated in this population, will be important for therapeutic decision making in women with HIV disease.

Reduction in recidivism of incarcerated women through primary care, peer counseling, and discharge planning.

Prior to release from the Rhode Island state prison, women at the highest risk for reincarceration and HIV infection are assigned to the Women's HIV/Prison Prevention Program (WHPPP), a discharge program designed to reduce the likelihood of reincarceration and HIV infection. Candidates for the WHPPP must meet at least one of three criteria: intravenous drug use or crack use, commercial sex work, or a history of prison recidivism with poor educational history and poor employment prospects. While incarcerated, the program participant develops a relationship with a physician and a social worker and establishes an individualized discharge plan. After release, the same physician and social worker continue to work with the client and assist an outreach worker in implementing the discharge plan. Data were collected from questionnaires administered to 78 women enrolled in the WHPPP between 1992 and 1995. The population in this program was primarily composed of ethnic minorities (55%), 25-35 years of age (55%), unmarried (90%), had children (72%), and displayed a variety of HIV risk behaviors. The WHPPP recidivism rates were compared with those of a mostly white (65%), similarly aged (51% were between 25 and 35 years of age) historical control group of all women incarcerated in Rhode Island in 1992. The intervention group demonstrated lower recidivism rates than the historical control group at 3 months (5% versus 18.5%, p = 0.0036) and at 12 months (33% versus 45%, p = 0.06). Assuming that recidivism is a marker for high-risk behavior, participation in the WHPPP was associated with a reduction in recidivism and in the risk of HIV disease in this very high risk group of women.

Exercise training has little effect on HDL levels and metabolism in men with initially low HDL cholesterol.

Low concentrations of high-density lipoprotein cholesterol (HDL-C) are a recognized risk factor for atherosclerotic cardiovascular disease. Exercise is often recommended to increase HDL-C, but the effect of exercise training on HDL levels and metabolism in subjects with low HDL concentrations is not well defined. The present study compared the HDL response to 12 months of supervised endurance exercise training without weight loss in 17 men aged 26 49 years with initially low ( < 40 mg/dl, N=7) or normal ( > 44 mg/dl, N=10) HDL-C levels. HDL-C levels and HDL apolipoprotein metabolism were assessed while the subjects consumed controlled diets before and after the year of training. Increases in total (5.1+/-2.8 versus 1.9+/-4.2 mg/dl, P=0.08) and HDL2 (3.8+/-2.9 versus 0.4+/-1.1 mg/dl, P=0.01) cholesterol were greater in men with normal initial HDL-C levels. Catabolic rates for HDL apolipoproteins decreased 7-14% and biological half-lives increased 10-15% after exercise training in subjects with normal HDL, but were unchanged in the low HDL-C group. HDL apolipoprotein synthetic rates were not consistently affected by exercise training in either group. Postheparin lipoprotein lipase activity increased 27%, the clearance rate of intravenous triglycerides increased 14%, and apolipoprotein B levels decreased 16% with training in subjects with normal HDL-C but were unchanged in the low HDL-C group. We conclude that the ability to increase HDL-C levels through endurance exercise training is limited in subjects with low initial HDL-C, possibly because exercise training in such subjects fails to alter triglyceride metabolism.

Effect of prolonged exercise training without weight loss on high-density lipoprotein metabolism in overweight men.

This study examined the effect of exercise training without weight loss on high-density lipoprotein (HDL) metabolism in overweight men. We evaluated HDL metabolism using 125I-radiolabeled autologous HDL in 17 overweight men aged 40 +/- 7 years (mean +/- SD) before and after 1 year of exercise training. Subjects consumed defined diets in a metabolic kitchen during the metabolic studies. They performed endurance exercise under supervision for 1 hour four times weekly and maintained their pretraining body weight. Maximal oxygen uptake (VO2max) increased 27% (P < .001) with exercise training. HDL-cholesterol (HDL-C) and apolipoprotein (apo) A-I increased 10% and 9%, respectively (P < .001 for both), whereas triglycerides and apo B decreased 7% and 10%, respectively (P < .05). Postheparin lipoprotein lipase increased 11% (P = NS). Hepatic triglyceride lipase activity (HTGLA) decreased 12% (P < .05). The fractional catabolic rate (FCR) of HDL protein and of apo A-I decreased 5% and 7%, respectively (P < .05 for both). The synthetic rate of apo A-I increased 13% (P < .01). Increased HDL after exercise training is associated with both decreased HDL protein catabolism and increased HDL apo A-I synthesis. Weight loss is not required to increase HDL-C with exercise training in overweight men, but without weight loss, even prolonged exercise training produces only modest changes in HDL-C concentrations.

Lipid and lipoprotein responses to episodic occupational and academic stress.

We examined the effects of psychological stress on plasma lipid, lipoprotein, and apolipoprotein levels in three related studies. In the first study, tax accountants (N = 20) and a comparable control group (N = 20) were assessed during and after the tax season. In the second and third studies, first-year medical students (N = 24 and N = 16) were assessed at midsemester and immediately before the examinations. Across studies, the stressors induced significant psychological distress. There were no corresponding changes in lipid and lipoprotein levels. Mean stress-induced change in total cholesterol level was -0.04 mmol/L (-1.6 mg/dL) (95% confidence interval, -0.23 to 0.16 mmol/L [-9 to 6 mg/dL]) for the accountants and 0 mmol/L (0 mg/dL) (95% confidence interval, -0.16 to 0.21 mmol/L [-6 to 8 mg/dL]) and 0.10 mmol/L (4 mg/dL) (95% confidence interval, -0.18 to 0.39 mmol/L [-7 to 15 mg/dL]) for medical students in the second and third studies, respectively. In all studies, change in total cholesterol level correlated with change in total serum protein levels (r = .42 to .60). These results suggest that commonly occurring stressful situations do not produce significant changes in plasma lipid and lipoprotein levels.

High density lipoprotein metabolism in endurance athletes and sedentary men.

BACKGROUND: Endurance athletes have higher high density lipoprotein (HDL) concentrations than sedentary controls. To examine the mechanism for this effect, we compared HDL apoprotein metabolism in 10 endurance athletes aged 34 +/- 6 years (mean +/- SD) and 10 sedentary men aged 36 +/- 8 years. METHODS AND RESULTS: Subjects were maintained on controlled diets for 4 weeks, and metabolic studies using autologously labeled 125I HDL were performed during the final 2 weeks. Lipids and lipoproteins were measured daily during these 2 weeks, and the average of 14 values was used in the analysis. HDL cholesterol (58 +/- 14 versus 41 +/- 10 mg/dl), HDL2 cholesterol (26 +/- 10 versus 12 +/- 8 mg/dl), and apolipoprotein A-I (apo A-I) (144 +/- 18 versus 115 +/- 22 mg/dl) were higher in the athletes, whereas triglyceride concentrations (60 +/- 18 versus 110 +/- 48 mg/dl) were lower (p less than 0.01 for all). Postheparin lipoprotein lipase activity was not different, but hepatic triglyceride lipase activity was 27% lower (p less than 0.06) in the athletes. The athletes' mean clearance rate of triglycerides after an infusion of Travamulsion (1 ml/kg) was nearly twofold that of the inactive men (5.8 +/- 1.5 versus 3.2 +/- 0.9%/min, p less than 0.001). There was no differences in HDL apoprotein synthetic rates, whereas the catabolic rates of both apo A-I (0.15 +/- 0.02 versus 0.22 +/- 0.05 pools per day, p less than 0.01) and apolipoprotein A-II (apo A-II) (0.15 +/- 0.02 versus 0.20 +/- 0.04 pools per day, p less than 0.05) were reduced in the trained men. Apo A-I and apo A-II half-lives correlated with HDL cholesterol in each group (r greater than 0.76, p less than 0.05 for all) but not consistently with lipase activities or fat clearance rates. This relation between apoprotein catabolism and HDL cholesterol was strongest at HDL cholesterol concentrations of less than 60 mg/dl. CONCLUSIONS: We conclude that higher HDL levels in active men are associated with increased HDL protein survival. The mechanisms mediating this effect require better definition, and other factors appear to contribute to HDL cholesterol and protein concentrations among individual subjects.

Determination of postmortem interval by arthropod succession: a case study from the Hawaiian Islands.

A postmortem interval of 34 to 36 days was established for remains recovered on the island of Oahu, Hawaii, based on interpretations of patterns of arthropod succession on the remains. This interval was primarily based on the presence of adult specimens of Philonthus longicornis (family Staphylinidae), mature larvae of Piophila casei (family Piophilidae), and empty puparial cases of Chrysomya rufifacies (family Calliphoridae). Species and developmental stages of two additional Coleoptera species and three additional Diptera species were also present, which was consistent with the estimated interval, although not definitive.

Bile salt-induced intracellular Ca++ accumulation in type II pneumocytes.

The pathogenesis of pneumonitis associated with meconium aspiration is poorly understood. To explore the possibility of pulmonary cytotoxicity in association with bile salt exposure and calcium accumulation, we compared cell viability, radiolabeled calcium accumulation, and intracellular [calcium] in the presence and absence of bile salts, chenodeoxycholate, and 3 beta-OH-5-cholenoate. We assessed viability of type II pneumocytes in culture by cell permeability to trypan blue dye, incorporation of leucine into cellular proteins, and cellular morphology. Intracellular calcium concentrations were monitored with fluorescent dye methodology. At micromolar concentrations, the above bile salts increased cell permeability by as much as 9-fold and decreased leucine incorporation by as much as 5-fold. Radiolabeled calcium accumulation increased by as much as 2.5-fold and intracellular [calcium] transiently increased by as much as 6-fold. Studies using bile salts extracted from meconium yielded similar results. Correlation of calcium accumulation to viability studies yielded a direct relationship with cell permeability and an inverse relationship with leucine incorporation. We speculate that bile salt-induced accumulation of intracellular calcium in lung cells may contribute to the pathogenesis of meconium aspiration pneumonitis.

Modest changes in high-density lipoprotein concentration and metabolism with prolonged exercise training.

High-density lipoprotein (HDL) metabolism was studied in eight sedentary men before and after 14 and 32-48 weeks of exercise training. Subjects rode stationary bicycles 1 hour daily, 5 days each week for 14 weeks (n = 8), and 4 days each week thereafter for a total of 32-48 weeks (n = 7) of training. HDL metabolism was assessed with 125I-radiolabeled autologous HDL while subjects consumed defined diets. Maximal oxygen uptake increased 26 +/- 7% (p less than 0.001) after 14 weeks but did not increase further with more prolonged training. Body weight and estimated body fat did not change. HDL cholesterol increased 5 +/- 3 mg/dl, and triglycerides decreased 19 +/- 23 mg/dl after 14 weeks (p less than 0.025 for both), but there were no additional changes with continued training. Postheparin plasma lipoprotein lipase activity was 22% higher than baseline activity after both 14 (p less than 0.025) and 32 or more weeks of exercise. In contrast, hepatic triglyceride lipase activity was 16 +/- 8% and 15 +/- 8% lower than baseline at each measurement (p less than 0.005 for both). The disappearance rate of triglycerides after an intravenously administered fat solution was 24 +/- 24% higher at 14 weeks and 49 +/- 18% (p less than 0.005) higher after more prolonged training. Total and low-density lipoprotein cholesterol and apolipoprotein A-I and A-II concentrations at the end of study were not different from initial values. Plasma volume was 8% above initial values at both post-training measurements. The biological half-life of apolipoprotein A-I was unchanged at 14 weeks but was 10 +/- 13% longer (p = 0.07) and increased in all but one subject at the end of the study. Half-life for apolipoprotein A-II was 8 +/- 8% (p = 0.031) and 11 +/- 14% (p = 0.06) above baseline at 14 and 32 or more weeks, respectively. The synthetic rates for apolipoproteins A-I and A-II were not different from baseline values at 32-48 weeks. We conclude that 8-11 months of exercise training in previously sedentary men enhances fat tolerance and increases HDL cholesterol concentrations by prolonging HDL survival. The changes in HDL apolipoprotein survival, however, do not approximate the differences previously noted between elite endurance athletes and sedentary men. Changes in HDL cholesterol concentration were not large and suggest that the potential for exercise-related changes in HDL may be modest in many subjects.

Limitations of red blood cell distribution width (RDW) in evaluation of microcytosis.

The red blood cell distribution width (RDW) has been proposed as an additional variable that would improve the initial classification of anemia. Microcytic anemias with an elevated RDW (greater heterogeneity) were used to distinguish iron deficiency from heterozygous thalassemia, which was said to have a normal RDW (more homogeneous). The authors attempted to classify their population of microcytic cases using the RDW as a major variable, but found only limited utility. While most of the iron-deficient cases had an increased RDW, almost one-half of the thalassemia cases also were classified as microcytic heterogeneous (increased RDW). The authors also found that target cells, erythrocytosis, and the ratios alone or in combination with the RDW were not specific in separating heterozygous thalassemia from iron deficiency. They conclude that a sequential evaluation (to include iron and hemoglobin studies) of cases of microcytosis is still needed.

18F positron emission computed tomography in closed head injury.

Locus and extent of cerebral dysfunction in five closed head injured patients as inferred from positron emission tomography (PET) and computed tomography (CT) scan studies were compared with locus and extent inferences made in the same five patients using three additional independent sources of data. These data included: (1) clinical neurologic examination findings, (2) an extensive battery of neuropsychologic tests (including WAIS, Wechsler Memory, Halstead Reitan procedures), and (3) a comprehensive speech and language assessment battery (including the Boston Diagnostic Aphasia Examination (BDAE) and the Token Test). Neurologic, psychologic, and speech examinations were conducted within one week of the PET and CT studies. Three patients were studied at three months, one patient at six months, and one patient at two years after head injury. Follow-up CT scans were done 14 months later on four of five patients. This study supported the following major conclusions: the PET findings closely correspond with the site and extent of cerebral dysfunction inferences derived from the neurologic and behaviorial examinations but the CT findings did not; the follow-up CT scans, however, showed structural abnormalities (ie, encephalomalacia and atrophy) that were consistent with the PET, neurologic examination, and behavioral assessment findings; the study strongly supports the validity and predictive utility of neurobehavioral data which are directly pertinent to rehabilitation planning/programming in patients with closed head injury.

Computerized tomography head scans as predictors of rehabilitation outcome.

This study explored the relationship between rehabilitation functional outcome, demographic characteristics, and predicted goal achievement for 30 patients with closed head injury according to characteristics of their computerized tomography (CT) head scans performed within 10 days of injury. Goals and outcome were measured according to levels of independent/dependent function at discharge from an interdisciplinary inpatient rehabilitation program by means of the Patient Evaluation Conference System (PECS). Patients were classified into the three following major subgroups according to CT findings: (1) normal; (2) 1 hemisphere lesion; and (3) bilateral lesion. Marked differences in patient outcome and in the team's ability to accurately predict outcome were found to match the subgroups so classified. The need to incorporate CT scan data into early team planning and goal setting is stressed.